The home of the Domus Galilaeana is in the ancient Palazzo della Specola, belonging to Pisa University. Built in 1734-35, this was the first public astronomical observatory in Tuscany. A high tower was expressly added to the building, raised on the remains of a previous one, but in 1826 it was demolished because unsafe. The University Library and the Chemistry Cabinet were also housed in this building.

The idea of creating an institution dedicated to Galileo Galilei and the study of his scientific works occurred during plans to celebrate the 100th anniversary of the First Meeting of Italian Scientists (Prima riunione degli scienziati italiani) held in Pisa in 1839: the Domus Galilaeana was constituted in 1941.

The building today houses a collection of 40.000 books and tracts, among which are a valuable and unique letter signed by Galileo Galilei containing the earliest formulation of the law of bodies in free fall (1604), and pictorial documents related to this Pisan scientist; the archives of Antonio Pacinotti, the inventor of the dynamo and the electric motor, the papers of Antonio Favaro, curator of the monumental national edition of Galileo’s works (1890-1909) and notes left by the physicists Enrico Fermi and Ettore Majorana are also here.

During its history, various scientific instruments belonging to other institutions have been kept in the Domus, among which Pacinotti’s "macchinetta" (little machine), the earliest model of an electric dynamo, and the CEP (Calcolatrice Elettronica Pisana - Pisan Electronic Calculator, now in the collection of the Museum of Calculating instruments). Scientific instruments closely related to archives are kept in the Domus, such as Fermi’s "Sorgenti", used in experiments on induced radioactivity, and the photographic apparatus of the astronomer Pio Emanuelli.